A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population
文献类型：期刊论文
| 作者 | Luo, Na1,2,3 ; Sui, Jing1,2,3,4,5,20; Chen, Jiayu4,5; Zhang, Fuquan6; Tian, Lin6; Lin, Dongdong4,5; Song, Ming1,2,3; Calhoun, Vince D.4,5,19; Cui, Yue1,2,3; Vergara, Victor M.4,5
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| 刊名 | EBIOMEDICINE
 |
| 出版日期 | 2018-11-01 |
| 卷号 | 37页码:471-482 |
| ISSN号 | 2352-3964 |
| 关键词 | Schizophrenia Multimodal fusion Genetic-brain-cognition pathway Working memory Mediation analysis |
| DOI | 10.1016/j.ebiom.2018.10.009 |
| 通讯作者 | Sui, Jing(jing.sui@nlpr.ia.ac.cn) ; Jiang, Tianzi(jiangtz@nlpr.ia.ac.cn) |
| 英文摘要 | Background: In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset. Methods: Gray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways. Findings: One linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance. Interpretation: This study has not only verified the impaired imaging-genetic association in schizophrenia,but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia. (C) 2018 The Authors. Published by Elsevier B.V. |
| WOS关键词 | INDEPENDENT COMPONENT ANALYSIS ; GRAY-MATTER ABNORMALITIES ; FUNCTIONAL CONNECTIVITY ; MULTIMODAL FUSION ; TEMPORAL GYRUS ; GENOMIC RISK ; ASSOCIATION ; MEMORY ; VOLUME ; LOCI |
| 资助项目 | Natural Science Foundation of China[81471367] ; Natural Science Foundation of China[61773380] ; Natural Science Foundation of China[31771076] ; Natural Science Foundation of China[91432302] ; Natural Science Foundation of China[91732305] ; Natural Science Foundation of China[31620103905] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDBS01040100] ; Science Frontier Program of the Chinese Academy of Sciences[QYZDJ-SSW-SMC019] ; National Key R&D Program of China[2017YFA0105203] ; Primary Research & Development Plan of Jiangsu Province[BE2016630] ; National Institute of Health[R56MH117107] ; National Institute of Health[R01EB005846] ; National Institute of Health[R01MH094524] ; National Institute of Health[P20GM103472] ; National Science Foundation[1539067] |
| WOS研究方向 | General & Internal Medicine ; Research & Experimental Medicine |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCIENCE BV |
| WOS记录号 | WOS:000451691900060 |
| 资助机构 | Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Science Frontier Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; Primary Research & Development Plan of Jiangsu Province ; National Institute of Health ; National Science Foundation |
| 源URL | [http://ir.ia.ac.cn/handle/173211/25695]  |
| 专题 | 自动化研究所_脑网络组研究中心 |
| 通讯作者 | Sui, Jing; Jiang, Tianzi |
| 作者单位 | 1.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Mind Res Network, Albuquerque, NM 87106 USA 5.LBERI, Albuquerque, NM 87106 USA 6.Wuxi Menial Hlth Ctr, Wuxi 214000, Peoples R China 7.Shanxi Med Univ, Clin Med Coll 1, Dept Psychiat, Hosp 1, Taiyuan 030000, Shanxi, Peoples R China 8.Xinxiang Med Univ, Dept Psychiat, Henan Mental Hosp, Affiliated Hosp 2, Xinxiang 453002, Peoples R China 9.Xinxiang Med Univ, Henan Key Lab Biol Psychiat, Xinxiang 453002, Peoples R China 10.Wuhan Univ, Dept Radiol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Luo, Na,Sui, Jing,Chen, Jiayu,et al. A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population[J]. EBIOMEDICINE,2018,37:471-482. |
| APA | Luo, Na.,Sui, Jing.,Chen, Jiayu.,Zhang, Fuquan.,Tian, Lin.,...&Jiang, Tianzi.(2018).A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population.EBIOMEDICINE,37,471-482. |
| MLA | Luo, Na,et al."A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population".EBIOMEDICINE 37(2018):471-482. |
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来源：自动化研究所
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